Reductions in albuminuria and in electrocardiographic left ventricular hypertrophy independently improve prognosis in hypertension: the LIFE study

BACKGROUND: In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, reduced urine albumin/creatinine ratio (UACR) as well as regression of left ventricular hypertrophy have been associated with lower incidence of cardiovascular events. We wanted to investigate whether these prognostic improvements were independent. METHODS: In 6679 hypertensive patients included in the LIFE study, we measured UACR, left ventricular hypertrophy by electrocardiography, serum cholesterol, plasma glucose and blood pressure after 2 weeks of placebo treatment and again after 1 year of anti-hypertensive treatment with either an atenolol- or a losartan-based regimen. During this first year of treatment, 77 patients encountered a non-fatal stroke or myocardial infarction and were excluded to avoid bias. During the next 3-4 years, 610 composite endpoints [cardiovascular death (n = 228), fatal or non-fatal myocardial infarction or stroke] were recorded. RESULTS: In Cox regression analyses, the composite endpoint was after adjustment for treatment allocation predicted by baseline logUACR [hazard ratio (HR) = 1.16 per 10-fold increase, P < 0.05], 1-year logUACR (HR = 1.29 per 10-fold increase), baseline Sokolow-Lyon voltage (HR = 1.01 per mm, both P < 0.001) and 1-year Cornell product (HR = 1.01 per 100 mm x ms, P < 0.01). Cardiovascular death was predicted by 1-year logUACR (HR = 1.59, P < 0.001), baseline Sokolow-Lyon voltage (HR = 1.01, P = 0.06) and 1-year Cornell product (HR = 1.02, P < 0.001). Both were predicted independent of age, Framingham risk score, current smoking, history of cardiovascular disease and diabetes. Gender, serum cholesterol, plasma glucose and blood pressure did not enter the models. CONCLUSIONS: Baseline UACR and Sokolow-Lyon voltage, as well as in-treatment UACR and Cornell product, added to the risk prediction independent of traditional risk factors, indicating that albuminuria and left ventricular hypertrophy reflect different aspects of cardiovascular damage and are modifiable cardiovascular risk factors.     

A blood pressure independent association between glomerular albumin leakage and electrocardiographic left ventricular hypertrophy. The LIFE Study. Losartan Intervention For Endpoint reduction

In the Losartan Intervention For Endpoint reduction (LIFE) study left ventricular (LV) hypertrophy was associated with increased urine albumin/creatinine ratio (UACR) at baseline. To evaluate whether this association was due only to parallel blood pressure (BP)-induced changes we re-examined the patients after 1 year of antihypertensive treatment to investigate whether changes in LV hypertrophy and UACR were related independently of changes in BP. In 7,142 hypertensive patients included in the LIFE study, we measured UACR, LV hypertrophy by electrocardiography, plasma glucose and BP after 2 weeks of placebo treatment and again after 1 year of antihypertensive treatment with either an atenolol or a losartan based regime. At baseline and still after 1 year of treatment logUACR (R = 0.28, P < 0.001) was still correlated to LV hypertrophy (beta = 0.05) assessed by ECG independently of systolic BP (beta = 0.16), plasma glucose (beta = 0.19) and age (beta = 0.08). Change in logUACR (R = 0.19, P < 0.001) during treatment was correlated to change in LV hypertrophy (beta = 0.10) independently of reduction in systolic BP (beta = 0.13) and change in plasma glucose (beta = 0.06). After 1 year of antihypertensive treatment UACR was still related to LV hypertrophy independently of systolic BP, and the reduction in UACR during that first year of treatment was related to regression of LV hypertrophy independently of reduction in systolic BP. This suggests that the relationship between LV hypertrophy and glomerular albumin leakage is not just due to parallel BP-induced changes. As glomerular albumin leakage may represent generalised vascular damage we hypothesise a vascular relationship between cardiac and glomerular damage.     

Population impact of losartan use on stroke in the European Union (EU): projections from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study

The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study was designed to compare losartan- vs atenolol-based antihypertensive treatment on cardiovascular morbidity and mortality in a population of 9193 hypertensive patients with left ventricular hypertrophy (LVH). In LIFE, the losartan-based treatment further reduced the primary composite end point (cardiovascular death, myocardial infarction, or stroke) by 13% (risk reduction (RR) 0.87, 95% confidence interval (CI) 0.77-0.98, P=0.021). The further reduction in stroke with losartan (RR 0.75, 95% CI 0.63-0.89, P=0.001) was the major contributing factor to the reduction in the primary end point. Our objective was to project the reduction in stroke observed with a losartan- vs an atenolol-based antihypertensive treatment regimen in the LIFE study to the European Union (EU) population. The number of stroke events averted was estimated by identifying the number of persons in the EU expected to meet the LIFE inclusion criteria, and multiplying this figure by the cumulative incidence risk difference in stroke from LIFE at 5.5 years. The age- and gender-specific prevalence of hypertension, electrocardiographically (ECG)-diagnosed LVH among those with hypertension (inclusion criteria), and heart failure among those with LVH and hypertension (exclusion criteria) were applied to the EU census estimates. We conservatively projected that an estimated 7.8 million individuals aged 55-80 years in the EU are affected by hypertension and ECG-diagnosed LVH. Use of a losartan-based antihypertensive treatment in this population is projected to prevent approximately 125 000 first strokes over a 5.5-year period. A population-wide prevention strategy of using losartan in patients with LVH and hypertension has the potential to have a major public health impact by reducing the morbidity and mortality of stroke in the EU.     

加强降压和血压变异性对高血压高危患者心血管事件的长期影响

目的观察加强降压治疗较常规治疗能否进一步降低高血压高危患者心脑血管事件的发生率,以及长期随诊血压变异性是否为心血管事件的危险因素。方法将763例患者随机进入强化治疗组（382例）和对照组（381例）。记录第4周、3个月、6个月及此后每6个月的血压值及主要终点事件。结果在平均4．5年随访期间,强化治疗组平均收缩压／舒张压为（133．8±6．6）／（79．7±5．5）mmHg,明显低于对照组[（151．7±12．7）／（87．7±8．0）mmHg,P〈0．001]。强化治疗组随诊收缩压和舒张压的标准差（SD）及收缩压和舒张压的变异系数（CV）均明显低于对照组。与对照组相比,强化治疗组的主要终点事件降低78％,致死和非致死性中风减少72％,总死亡率和心血管病死亡率分别降低64％和82％（P均〈0．001）。Cox回归分析显示年龄、最终收缩压和舒张压、收缩压和舒张压的标准差是终点事件发生的危险因素。结论强化降压治疗使血压降至132／80mmHg左右时可以显著地降低高血压高危患者心脑血管病事件的发病率和死亡率;长期随诊的血压变异性是高血压高危患者心脑血管病事件的危险因素。     

N-terminal brain natriuretic peptide predicted cardiovascular events stronger than high-sensitivity C-reactive protein in hypertension: a LIFE substudy

BACKGROUND: N-terminal pro-brain natriuretic peptide (Nt-proBNP) and high-sensitivity C-reactive protein (hsCRP) are cardiovascular risk markers in various populations, but are not well examined in hypertension. Therefore, we wanted to investigate whether high Nt-proBNP or hsCRP predicted the composite endpoint of cardiovascular death, non-fatal stroke or non-fatal myocardial infarction independently of traditional cardiovascular risk factors and the urine albumin: creatinine ratio (UACR), which is a well established cardiovascular risk factor in hypertension. METHODS: In 945 hypertensive patients from the LIFE study with electrocardiographic left ventricular (LV) hypertrophy, we measured traditional cardiovascular risk factors including electrocardiography, morning UACR, hsCRP by immunoturbidimetry assay and Nt-proBNP by immunoassay after 2 weeks of placebo treatment. During 55 months' follow-up 80 patients suffered a composite endpoint. RESULTS: HsCRP as well as Nt-proBNP above the median values of 3.0 mg/l and 170 pg/ml, respectively, was associated with a higher incidence of composite endpoint (13.1 versus 3.8%, P < 0.01, and 11.5 versus 5.4%, P < 0.01). In Cox regression analyses, standardized log(hsCRP)/SD predicted a composite endpoint [hazard ratio (HR) 1.3 per SD = 0.47 log(mg/l), P < 0.05] after adjustment for traditional cardiovascular risk factors, but not after further adjustment for UACR. Standardized log(Nt-proBNP)/SD predicted a composite endpoint after adjustment for traditional cardiovascular risk factors [HR 1.9 per SD = 0.49 log(pg/ml), P < 0.05] as well as after further adjustment for UACR [HR 1.5 per SD = 0.49 log(pg/ml), P < 0.01]. Log(Nt-proBNP) added significantly to the Cox regression models using traditional cardiovascular risk factors with and without UACR (both P < 0.001). CONCLUSION: Nt-proBNP predicted a composite endpoint after adjustment for traditional risk factors, UACR and a history of diabetes or cardiovascular disease and added significantly to the prediction of composite endpoint, whereas hsCRP did not.     

上海郊区非糖尿病人群中低水平清蛋白尿与肱踝脉搏波传导速度的相关性分析

目的:探讨上海郊区非糖尿病人群中低水平清蛋白尿与肱踝脉搏波传导速度(baPWV)的相关性。方法:在上海市嘉定区选取1 548名正常清蛋白尿[尿清蛋白/肌酐(UACR)     

An association of a variety of cardiovascular risk factors with low grade albuminuria in Korean men

BackgroundsRecent studies have challenged the original definition of microalbuminuria when used to assess the risk of coronary heart disease or death. However, no large study has been conducted on Asian subjects regarding this topic to date. Therefore, we investigated the relationship between albuminuria below 17 μg/mg and other cardiovascular risk factors in apparently healthy Korean men.MethodsWe enrolled 2474 men with albuminuria below 17 μg/mg to participate in this study. We evaluated a variety of cardiovascular risk factors as well as the urine albumin creatinine ratio (UACR). The subjects were stratified into five groups by their UACR values and comparisons were made among the five groups.ResultsThe comparisons showed that the UACR was progressively higher in subjects with a larger waist circumference and BMI as well as higher values for: serum triglyceride, glucose, hsCRP, and the systolic BP, in addition to a higher prevalence of diabetes and metabolic syndrome. When we excluded subjects with hypertension and diabetes, the results were similar.ConclusionsOur findings suggest that low grade albuminuria in Korean men was associated with a variety of cardiovascular risk factors, and this finding was unchanged when we excluded subjects with diabetes and hypertension. Further studies are warranted to evaluate the clinical implications of our findings.     

Correlates of pulse pressure reduction during antihypertensive treatment (losartan or atenolol) in hypertensive patients with electrocardiographic left ventricular hypertrophy (the LIFE study)

In hypertensive patients, pulse pressure has been related to hypertension-induced target organ damage and risk of cardiovascular events. However, correlates of pulse pressure reduction during antihypertensive treatment have been less extensively investigated. We related pulse pressure changes to clinical and echocardiographic findings before and after 2 years of antihypertensive treatment in 767 patients aged 55 to 80 years (mean 66) in the Losartan Intervention For End point reduction in hypertension study. Over 2 years, blood pressure and pulse pressure were reduced from 173/98 to 147/84 mm Hg and from 75 to 63 mm Hg, respectively, both p <0.001. In linear multivariate analysis controlling for initial pulse pressure, 2-year reduction in pulse pressure correlated negatively with age and concomitant diabetes mellitus, and positively with body height and 2-year reduction in mean blood pressure (multiple R(2) = 0.42, p <0.01). When dividing the study population into 2 groups using a prognostically validated partition for pulse pressure, patients with pulse pressure > or =63 mm Hg after 2 years of antihypertensive treatment (n = 349) were older and shorter, included more women and patients with isolated systolic hypertension, diabetes mellitus, albuminuria, and echocardiographic left ventricular hypertrophy at baseline, and also had a smaller decrease in mean blood pressure and the urinary albumin/creatinine ratio over 2 years (all p <0.05). Thus, in hypertensive patients with electrocardiographic left ventricular hypertrophy, older age, less reduction in mean blood pressure, concomitant diabetes mellitus, and shorter stature are associated with attenuated pulse pressure reduction during antihypertensive treatment.     

Rationale for and study design of the sulodexide trials in Type 2 diabetic, hypertensive patients with microalbuminuria or overt nephropathy.

BACKGROUND: Patients with Type 2 diabetes and albuminuria are at high risk to progress to end-stage renal disease (ESRD). Although angiotensin receptor blockers confer renoprotection, many diabetic patients still develop overt nephropathy and reach ESRD. Glycosaminoglycans belong to the same family as heparin and heparinoids. Pilot studies with sulodexide, a glycosaminoglycan, have shown that sulodexide can reduce urinary albumin excretion rates in diabetic patients. No hard renal end-point data are available. METHODS: Two multicentre, double-masked, randomized placebo controlled trials were designed to study the renoprotective potential of sulodexide. The Sulodexide Microalbuminuria Trial examined the efficacy of sulodexide given over 26 weeks in 1000 patients with Type 2 diabetes, hypertension and microalbuminuria. The Sulodexide Overt Nephropathy Trial examined the efficacy of sulodexide in 2240 patients with Type 2 diabetes, hypertension and proteinuria > or = 900 mg/24 h. RESULTS: The primary outcome of The Sulodexide Microalbuminuria Trial was (i) conversion to normoalbuminuria and at least a 25% decrease in the urinary albumin creatinine ratio (UACR), or (ii) at least a 50% reduction in UACR. The primary outcome of The Sulodexide Overt Nephropathy Trial was time to a composite end point of doubling of serum creatinine or ESRD. CONCLUSIONS: The sulodexide nephropathy programme will document whether therapy with sulodexide confers renal protection in Type 2 diabetes and nephropathy.     

Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in hypertension with left ventricular hypertrophy? A LIFE substudy

OBJECTIVES: To examine a possible relationship between baseline albuminuria and effect of losartan versus atenolol on cardiovascular (CV) events in hypertensive patients with left ventricular hypertrophy, the effect of losartan versus atenolol on albuminuria, and whether the benefits of losartan versus atenolol could be explained by influence of losartan on albuminuria. DESIGN: Double-blind, randomized, controlled trial of 4.8 years. SETTING: Out-patient setting. PATIENTS: A total of 8206 with hypertension and left ventricular hypertrophy. INTERVENTIONS: Losartan or atenolol, supplemented with diuretics and/or calcium antagonists to reach blood pressure < 140/90 mmHg MAIN OUTCOME MEASURES: The urine albumin/creatinine ratio, and the primary composite endpoint (CEP) of CV death, myocardial infarction, and stroke. RESULTS: The blood pressure was reduced similarly on losartan (30.2/16.6 mmHg) versus atenolol (29.1/16.8 mmHg). The risk of a primary CEP increased linearly from the lowest to the highest decile of baseline albuminuria. The benefits of losartan versus atenolol for the primary CEP and for stroke tended to be more pronounced among patients above the median value for baseline albuminuria (urine albumin/creatinine ratio, 1.28 mg/mmol). The decrease in albuminuria was significantly greater with losartan versus atenolol throughout the study (a decrease from baseline to year 2 of 33% losartan versus 25% atenolol). One-fifth of the difference in favor of losartan on the primary CEP was explained by the greater reduction in albuminuria on losartan. CONCLUSIONS: Baseline albuminuria is a powerful risk factor for CV events. Baseline albuminuria did not identify the group of patients with greatest benefit on losartan versus atenolol in LIFE. Reduction in albuminuria explained one-fifth of the benefits of losartan versus atenolol.     

G-protein beta3-subunit gene 825T allele and hypertension: a longitudinal study in young grade I hypertensives

The 825T allele of the GNB3 gene has been associated with essential hypertension and obesity in cross-sectional studies. We have therefore planned a longitudinal cohort study to assess whether the GNB3 825T allele is predictive of blood pressure increase in young subjects with grade I hypertension. We genotyped at the GNB3 825 locus 461 participants of the Hypertension and Ambulatory Recording Venetia Study (HARVEST) study (age, 18 to 45 years) at low cardiovascular risk, according to 1999 ISH/WHO criteria. The study end point was eligibility for antihypertensive medication, that is, progression to grade II hypertension during the first year of observation or office systolic blood pressure > or =150 mm Hg and/or office diastolic blood pressure > or =95 mm Hg in two later consecutive visits during follow-up. At baseline, there was no statistically significant difference among genotypes with respect to body mass index, blood pressure, and heart rate. During follow-up (mean, 4.7 years), 113 (51.1%) patients with CC genotype and 145 (60.4%) patients with TT/TC genotype reached the end point. According to survival analysis, the patients carrying the 825T allele had an increased risk of reaching the blood pressure end point (CI, 1.108 to 1.843; P=0.006). In young patients with grade I hypertension, the 825T allele is associated with increased risk of progression to more severe hypertension requiring antihypertensive therapy. The GNB3 825T allele may be considered a genetic marker of predisposition for hypertension.     

Relation of reduction in urinary albumin excretion to ten-year cardiovascular mortality in patients with type 2 diabetes and systemic hypertension

Microalbuminuria is one of the strongest predictors of both adverse renal and cardiovascular disease (CVD) outcomes in patients with type 2 diabetes mellitus. Although measurement of urinary albumin excretion (UAE) is widely recommended, limited data are available to suggest that reducing UAE translates into a reduction in long-term cardiovascular mortality, particularly among patients without overt nephropathy, who constitute most patients with type 2 diabetes worldwide. We assessed whether changes in the UAE at 1 year were associated with cardiovascular mortality in 393 patients with hypertension and type 2 diabetes during a 10-year period. On univariate analysis, CVD history, age, diabetes duration, and change in UAE at 1 year were associated with cardiovascular mortality risk (hazard ratio 2.60 for those with CVD history, 95% confidence interval [CI] 1.47 to 4.62; hazard ratio 1.59 per 10 years of diabetes duration, 95% CI 1.12 to 2.25; and hazard ratio 1.49 per log UAE increase, 95% CI 1.13 to 1.96). In a stepwise Cox regression model that included baseline UAE and CVD history, the 10-year predicted mortality of those with a decrease in UAE of 2 logs at 1 year was 4.7% (95% CI 1.4% to 7.8%). For those with an increase in UAE of 2 logs at 1 year, it was 24.5% (95% CI 10.1% to 36.5%). In conclusion, these data support current guideline recommendations to screen for UAE in all patients with type 2 diabetes, even in the absence of nephropathy, and suggest that serial UAE measurements even after the initiation of antihypertensive therapy has prognostic value independent of traditional cardiovascular risk factors.     

Aggressive blood pressure-lowering therapy guided by home blood pressure monitoring improves target organ damage in hypertensive patients with type 2 diabetes/prediabetes

J Clin Hypertens (Greenwich). 2012; 14:422–428. ©2012 Wiley Periodicals, Inc. The authors tested the hypothesis that an aggressive antihypertensive treatment is beneficial in protecting against target organ damage (TOD) in patients with type 2 diabetes/prediabetes. The authors enrolled 60 patients with uncontrolled hypertension and diabetes/prediabetes and performed clinic, home, and ambulatory blood pressure (BP) monitoring. Irbesartan, amlodipine, and indapamide were used according to a titration schedule from step 1 to 5 for target home BP level ≤125/75 mm Hg. The flow‐mediated vasodilation (FMD), radial augmentation index (AI), pulse wave velocity (PWV), and urinary albumin excretion ratio (UACR), as a surrogate marker of TOD, were measured at baseline and 6 months. Compared with baseline, clinic, home, and ambulatory BP measures were significantly lower in the sixth month. FMD was increased significantly and AI, PWV, and UACR were reduced by the treatment. The extent of the changes in PWV and UACR were associated with the changes in all BP measures, but only the change in home morning BP was associated with the change in FMD. The change in AI was not associated with the change in BP levels, but was associated with the change in PWV. A very aggressive antihypertensive therapy guided by home morning BP was effective for surrogate end points in patients with diabetes/prediabetes.     

Pulse pressure is an independent determinant of renal function decline during treatment of essential hypertension

BACKGROUND: In large epidemiological studies and using serum creatinine or estimates of glomerular filtration rate (GFR), blood pressure has emerged as a predominant determinant of the age-associated decline in renal function. METHODS: The present longitudinal study (median follow-up period of 5.8 years) was conducted in 132 never-treated patients with essential hypertension at baseline. The effect of treatment on the GFR and effective renal plasma flow, estimated by urinary clearances of isotopic markers, was assessed. RESULTS: Satisfactory control of hypertension (<140/90 mmHg) was achieved in 57% of the population. During follow-up, the yearly change in the GFR was -1.72+/-0.21 ml/min per year (mean+/-SEM). In univariate regression analysis, the change in the GFR was correlated with baseline pulse pressure (r=-0.27, P=0.002), whereas no influence of systolic, diastolic or mean blood pressures, as well as baseline albuminuria or left ventricular mass index, was found. Multivariate logistic regression analysis showed that only baseline pulse pressure conveyed a significant odds ratio of accelerated decline of GFR (>median of 1.5 ml/min per year), independently of age, baseline GFR, mean blood pressure and other known cardiovascular risk factors. No influence of the type of antihypertensive treatment (64% of the population had received angiotensin-converting enzyme inhibitor) was detected. CONCLUSION: Pulse pressure (a marker of arterial stiffening) is suggested as an independent determinant of the treatment-associated decline in renal function in essential hypertension. No influence of target organ damage (albuminuria of left ventricular hypertrophy) was detected.     

New risk markers may change the HeartScore risk classification significantly in one-fifth of the population

The study aim was to determine whether urine albumin/creatinine ratio (UACR), high-sensitivity C-reactive protein (hsCRP) or N-terminal pro-brain natriuretic peptide (Nt-proBNP) added to risk prediction based on HeartScore and history of diabetes or cardiovascular disease. A Danish population sample of 2460 individuals was divided in three groups: 472 subjects receiving cardiovascular medication or having history of diabetes, prior myocardial infarction or stroke, 559 high-risk subjects with a 10-year risk of cardiovascular death above 5% as estimated by HeartScore, and 1429 low-moderate risk subjects with estimated risk below 5%. During the following 9.5 years the composite end point of cardiovascular death, non-fatal myocardial infarction or stroke (CEP) occurred in 204 subjects. CEP was predicted in all three groups by UACR (HRs: 2.1, 2.1 and 2.3 per 10-fold increase, all P<0.001) or by hsCRP (HRs: 1.9, 1.9 and 1.7 per 10-fold increase, all P<0.05), but not by Nt-proBNP (HRs: 1.1, 2.6 and 3.7 per 10-fold increase, last two P<0.001) (P<0.05 for interaction). In the low-moderate risk group, pre-specified gender adjusted (men/women) cutoff values of UACR> or =0.73/1.06 mg mmol(-1) or hsCRP> or =6.0/7.3 mg l(-1) identified a subgroup of 16% who experienced one-third of the CEPs. In the patient group, combined absence of high UACR and high Nt-proBNP> or =110/164 pg ml(-1) (men/women) identified a subgroup of 52% who experienced only 15% of the CEPs. Additional use of UACR and hsCRP in subjects with low-moderate risk and UACR and Nt-proBNP in subjects with known diabetes of cardiovascular disease changed HeartScore risk classification significantly in 19% of the population.     

Effect of once-weekly exenatide on estimated glomerular filtration rate slope depends on baseline renal risk: A post hoc analysis of the EXSCEL trial

The effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on renal outcomes in patients with type 2 diabetes at high cardiovascular risk are modest or neutral. However, GLP-1RAs may confer clinical benefits in those at high risk of progressive renal function loss. We examined the effects of once-weekly exenatide (EQW) on estimated glomerular filtration rate (eGFR) slope and urinary albumin:creatinine ratio (UACR) as a function of baseline UACR in 3503 EXSCEL participants (23.7%) with eGFR data available and 2828 participants (19.2%) with UACR change data available. EQW improved eGFR slope assessed via mixed model repeated measures, compared with placebo, in participants with baseline UACR >100 mg/g (0.79 mL/min/1.73 m²/year [95% confidence interval {CI} 0.24–1.34]) and UACR >200 mg/g (1.32 mL/min/1.73 m²/year [95% CI 0.57–2.06]), but not at lower UACR thresholds. EQW reduced UACR, compared with placebo, assessed via analysis of covariance, consistently across subgroups with baseline UACR >30 mg/g (28.2% reduction), baseline UACR >100 mg (22.5% reduction) and baseline UACR >200 mg (34.5% reduction). This post hoc EXSCEL analysis suggests that EQW reduces UACR, with improvement in eGFR slope specifically in participants with elevated baseline UACR.     

Left atrial size and risk of major cardiovascular events during antihypertensive treatment: losartan intervention for endpoint reduction in hypertension trial

The influence of left atrial size on cardiovascular events during antihypertensive treatment has not been reported previously from a long-term, prospective, randomized hypertension treatment trial. We recorded left atrial diameter by annual echocardiography and cardiovascular events in 881 hypertensive patients (41% women) with electrocardiographic left ventricular hypertrophy aged 55 to 80 (mean: 66) years during a mean of 4.8 years of randomized losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint Reduction in Hypertension Study. During follow-up, a total of 88 primary end points (combined cardiovascular death, myocardial infarction, or stroke) occurred. In Cox regression, baseline left atrial diameter/height predicted incidence of cardiovascular events (hazard ratio: 1.98 per cm/m [95% CI: 1.02 to 3.83 per cm/m]; P=0.042) adjusted for significant effects of Framingham risk score and history of atrial fibrillation. Greater left atrial diameter reduction during follow-up was associated with greater reduction in left ventricular hypertrophy, absence of new-onset atrial fibrillation or mitral regurgitation during follow-up, and losartan-based treatment (B=-0.13+/-0.03 cm/m; P<0.001) in multiple linear regression, adjusting for baseline left atrial diameter/height. However, in time-varying Cox regression analysis, left atrial diameter reduction was not independent of left ventricular hypertrophy regression in predicting cardiovascular events during follow-up. In conclusion, left atrial diameter/height predicts risk of cardiovascular events independent of other clinical risk factors in hypertensive patients with left ventricular hypertrophy and may be useful in pretreatment clinical assessment of cardiovascular risk in these patients.     

Cardiovascular events in subgroups of patients during primary treatment of hypertension with candesartan or losartan

Merging data from existing electronic patient records, and electronic hospital discharge and cause of death registers, is a fast and relatively inexpensive method for comparing different treatments with regard to clinical outcome. This study compared the effects of antihypertensive treatment with candesartan or losartan on cardiovascular disease (CVD) using Swedish registers. Patients without previous CVD who were prescribed candesartan (n=7329) or losartan (n=6771) for hypertension during 1999-2007 at 72 Swedish primary care centers were followed for up to 9 years. Both medications were given according to current recommendations, and there was no difference observed in achieved blood pressures. The authors have previously shown that candesartan lowered the risk of all CVD (primary composite end point) more so than losartan (adjusted hazard ratio, 0.86; 95% confidence interval, 0.77-0.96). Candesartan also had a significantly better effect with regards to reducing the development of heart failure, cardiac arrhythmias, and peripheral arterial disease. In the present analysis, the authors found that candesartan, compared with losartan, reduced the risk of all CVD, irrespective of sex, age, previous antihypertensive treatment, baseline blood pressure, and presence of diabetes. These clinical findings may reflect differences between candesartan and losartan in their binding characteristics to the angiotensin type 1 receptor.     

Triglyceride-high-density lipoprotein cholesterol is associated with microvascular complications in type 2 diabetes mellitus

The purpose of this study was to evaluate whether a high triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio is associated with an increased incidence of retinopathy and chronic kidney disease (CKD) in type 2 diabetes mellitus. Individuals with type 2 diabetes mellitus (n = 979) with an estimated glomerular filtration rate greater than 60 mL/min and without retinopathy and cardiovascular disease at baseline were followed up for the incidence of diabetic retinopathy (diagnosed by retinography) and CKD (diagnosed by estimated glomerular filtration rate ≤60 mL/min/1.73 m(2)). On follow-up (mean, 4.9 years), 217 (22.2% of total) subjects experienced CKD and/or diabetic-specific retinal lesions (microvascular complication). Of these, 111 subjects developed isolated retinopathy, 85 developed CKD alone, and 21 developed both complications. The TG/HDL-C ratio was positively associated with an increased risk of incident retinopathy and/or CKD (composite microvascular end point) independently of age, sex, body mass index, diabetes duration, hemoglobin A(1c), hypertension, smoking history, low-density lipoprotein cholesterol, albuminuria, and current use of hypoglycemic, antihypertensive, lipid-lowering, or antiplatelet drugs (multivariable-adjusted odds ratio, 2.15; 95% confidence intervals, 1.10-4.25; P = .04). These findings suggested that the TG/HDL-C ratio was associated with an increased incidence of microvascular complications in individuals with type 2 diabetes mellitus without prior cardiovascular disease, independently of several potential confounders.